Reduced expression of Raf-1 kinase inhibitory protein in renal cell carcinomaa: a significant prognostic marker

Moon, Ahrim; Park, Jae Young; Sung, Ji Youn; Park, Yong-Koo; Kim, Youn Wha

doi:10.1097/pat.0b013e32835817e8

Cited by 23 publications

(19 citation statements)

References 29 publications

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“…Low RKIP expression or its loss associates with the onset and development of gastric cancers and its ability to invade and metastasize [57,221], as well as with recurrence in esophageal squamous cell carcinoma (ESCC) [222], malignant progression in hepatic fibrosis [223], and poor survival in gastric cancer [224,225]. RKIP loss also serves as a predictive marker for the progression and metastasis of liver [226,227], kidney [228], breast [229], ovarian [230], and colorectal cancers [231], as well as pancreatic ductal adenocarcinoma (PDAC) [232]. Combined with its promoter’s methylation, RKIP expression was further suggested as a biomarker of ESCC [233].…”

Section: Rkip As a Prognostic Indicator And A Therapeutic Targetmentioning

confidence: 99%

RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact

Zaravinos

Bonavida

Chatzaki

et al. 2018

Cancers

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RAF-kinase inhibitor protein (RKIP) is a well-established tumor suppressor that is frequently downregulated in a plethora of solid and hematological malignancies. RKIP exerts antimetastatic and pro-apoptotic properties in cancer cells, via modulation of signaling pathways and gene products involved in tumor survival and spread. Here we review the contribution of RKIP in the regulation of early metastatic steps such as epithelial–mesenchymal transition (EMT), migration, and invasion, as well as in tumor sensitivity to conventional therapeutics and immuno-mediated cytotoxicity. We further provide updated justification for targeting RKIP as a strategy to overcome tumor chemo/immuno-resistance and suppress metastasis, through the use of agents able to modulate RKIP expression in cancer cells.

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Section: Rkip As a Prognostic Indicator And A Therapeutic Targetmentioning

confidence: 99%

RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact

Zaravinos

Bonavida

Chatzaki

et al. 2018

Cancers

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“…The role of RKIP has been assessed in hepatocellular carcinoma (HCC), in which its expression was significantly reduced, likely accounting for the hyper‐activation of ERK cascade in human HCC (Schuierer et al, 2006; Xu et al, 2010; Notarbartolo et al, 2011; Walker et al, 2011; Wu et al, 2011). RKIP expression was also diminished in pancreatic cancer (Kim et al, 2010; Song et al, 2012), cancer of the ampulla of Vater (Kim et al, 2012a), non‐melanocytic skin cancers (Libra and Torrisi, 2009; Zaravinos et al, 2009), esophageal cancer (Birner et al, 2012; Gao et al, 2012; Guo et al, 2012a; Kim et al, 2012b), gastrointestinal stromal tumors (Martinho et al, 2009) and its response to Imatinib (Valadao et al, 2012), gastric cancers (Fujimori et al, 2012; Jia et al, 2012; Guo et al, 2012a; Zhang et al, 2013), renal cell carcinoma (Moon et al, 2012), endometrial cancer (Martinho et al, 2012a), and brain tumors (Gimenez et al, 2010; Maresch et al, 2011; Martinho et al, 2012b). In breast cancer, lymph node metastases displayed significantly reduced levels of RKIP (Hagan et al, 2005; Minn et al, 2012).…”

Section: Clinical Significance Of Rkip and Prkip Perturbationmentioning

confidence: 99%

RKIP: Much more than Raf Kinase inhibitory protein

Al-Mulla

Bitar

Taqi

et al. 2013

Journal Cellular Physiology

115

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From its discovery as a phosphatidylethanolamine-binding protein in bovine brain to its designation as a physiological inhibitor of Raf kinase protein, RKIP has emerged as a critical molecule for maintaining subdued, well-orchestrated cellular responses to stimuli. The disruption of RKIP in a wide range of pathologies, including cancer, Alzheimer's disease, and pancreatitis, makes it an exciting target for individualized therapy and disease-specific interventions. This review attempts to highlight recent advances in the RKIP field underscoring its potential role as a master modulator of many pivotal intracellular signaling cascades that control cellular growth, motility, apoptosis, genomic integrity, and therapeutic resistance. Specific biological and functional niches are highlighted to focus future research towards an enhanced understanding of the multiple roles of RKIP in health and disease.

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“…Collectively, these researches suggest that RKIP may act as not only an inhibitor of tumorigenesis, but also a metastasis suppressor. In addition, Moon and his colleagues suggested that RKIP expression was a significant prognostic marker for RCC and its level was tightly associated with progression and metastasis in renal cancer [22] . Recently, a study of 310 RCC cases has suggested RKIP was a significant prognostic marker because of its close correlation with progression and metastasis of RCC.…”

Section: Introductionmentioning

confidence: 99%

Genetic Variants in RKIP Are Associated with Clear Cell Renal Cell Carcinoma Risk in a Chinese Population

et al. 2014

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BackgroundRaf-1 kinase inhibitor protein (RKIP) plays a critical role in tumor development by regulating cell functions such as invasion, apoptosis and differentiation. Down-regulation of RKIP expression has been implicated in the development and progression of renal cell carcinoma (RCC). Herein, we hypothesized that genetic polymorphisms in RKIP might be associated with susceptibility and progression of RCC.MethodsA total of 5 tagging single-nucleotide polymorphisms (tSNPs) in RKIP were selected and genotyped by SNapShot method in a case-control study of 859 RCC patients and 1004 controls. The logistic regression was used to evaluate the genetic association with occurrence and progression of RCC. The functionality of the important SNP was preliminary examined by qRT-PCR.ResultWe found that the rs17512051 in the promoter region of RKIP was significantly associated with decreased clear cell RCC (ccRCC) risk (TA/AA vs. TT: P = 0.039, OR = 0.78, 95%CI = 0.62–0.99). Another SNP (rs1051470) in the 3′UTR region of RKIP was marginally associated with increased ccRCC risk (TT vs. CC+CT: OR = 1.45, 95%CI = 1.01–2.09). In the stratified analysis, the protective effect of rs17512051 was more predominant in the subgroups of male, non-smokers, non-drinkers as well as subjects without history of diabetes. Furthermore, we observed higher RKIP mRNA levels in the presence of the rs17512051A allele in normal renal tissues.ConclusionOur results suggest that the potentially functional RKIP rs17512051 polymorphism may affect ccRCC susceptibility through altering the endogenous RKIP expression level. Risk effects and the functional impact of this polymorphism need further validation.

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Reduced expression of Raf-1 kinase inhibitory protein in renal cell carcinomaa: a significant prognostic marker

Cited by 23 publications

References 29 publications

RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact

RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact

RKIP: Much more than Raf Kinase inhibitory protein

Genetic Variants in RKIP Are Associated with Clear Cell Renal Cell Carcinoma Risk in a Chinese Population

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